Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics, predictive factors and impact on post‐transplant outcome

Elkaim, Élodie; Picard, Christophe; Garrigue, Claire; Barlogis, Vincent; Loundou, Anderson; Curtillet, Catherine; Oudin, Claire; Thuret, Isabelle; Chambost, Hérvè; Gautier, Michel

doi:10.1111/bjh.12918

Cited by 15 publications

(14 citation statements)

References 28 publications

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“…Significant recipient chimerism is associated with a higher frequency of donor tolerance [9, 10] and could affect the interpretation of chronic GVHD biomarkers when donor-derived hematopoiesis is not fully engrafted. In patients with questionable engraftment, chimerism should be examined, and the patient should be excluded from biomarker studies if results show < 90% donor chimerism, ideally in either lymphoid or myeloid populations.…”

Section: Risk Factors and Covariates To Considermentioning

confidence: 99%

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report

Paczesny

Hakim

Pidala

et al. 2015

Biology of Blood and Marrow Transplantation

127

125

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Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic GVHD after allogeneic hematopoietic cell transplantation (HCT) or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include: a) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity, b) prognostic risk to develop chronic GVHD, and c) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well-documented following established quality control guidelines for sample acquisition, processing, preservation and testing, at intervals that are both calendar- and event-driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for utilization in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a four-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines.

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Section: Risk Factors and Covariates To Considermentioning

confidence: 99%

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report

Paczesny

Hakim

Pidala

et al. 2015

Biology of Blood and Marrow Transplantation

127

125

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“…Consensus is still missing on the best cut-off value for positivity in qPCR as well as the preferable use of bone marrow (BM) or peripheral blood (PB), the latter with obvious logistical advantages for sample acquisition at sufficiently high abundance but with potentially lower informative value compared with BM, the natural environment for relapse onset. Moreover, only a single report has to our knowledge so far addressed the question of engraftment monitoring by qPCR, in the particular setting of umbilical cord blood SCT [44]. Possibly because of the still limited available evidence for its clinical utility, most clinical laboratories still do not use qPCR for routine chimerism testing but prefer STR as the standard method.…”

Section: Introductionmentioning

confidence: 99%

Clinical Utility of Quantitative PCR for Chimerism and Engraftment Monitoring after Allogeneic Stem Cell Transplantation for Hematologic Malignancies

Ahci

Stempelmann

Buttkereit

et al. 2017

Biology of Blood and Marrow Transplantation

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Although quantitative PCR (qPCR) has been explored for chimerism monitoring after allogeneic stem cell transplantation (SCT), evidence regarding its clinical utility compared with standard short tandem repeat (STR) is still limited. We retrospectively studied commercial qPCR and STR chimerism with respective positivity thresholds of .1% and 1% in 359 peripheral blood (PB) and 95 bone marrow (BM) samples from 30 adult patients after first HLA-matched SCT for myeloid malignancies or acute lymphatic leukemia. Concordance between the 2 methods was 79.5%, with all discordant samples positive in qPCR but negative in STR. Of the latter, sporadic qPCR positivity without clinical correlates was seen mostly in BM samples early post-transplant. In 7 of 21 patients with available follow-up samples in the first months after transplantation, qPCR but not STR revealed low levels (<1%) of sustained host chimerism in PB, reflecting delayed engraftment or persistent mixed chimerism (PMC). These conditions were associated with donor-recipient cytomegalovirus (CMV) serostatus and early CMV reactivation but not with immunosuppressive regimens or clinical outcome. qPCR predicted all 8/8 relapses with samples in the 6 months before onset by sustained positivity in both PB and BM compared with 1/8 relapses predicted by STR mainly in BM. The response kinetics to donor lymphocyte infusions for the treatment of PMC or relapse was shown by qPCR but not STR to be protracted over several months in 3 patients. Our results demonstrate the superior clinical utility of qPCR compared with STR for monitoring subtle changes of host chimerism associated with different clinical conditions, making a case for its use in the clinical follow-up of transplant patients.

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“…Two recent studies found that the incidences of cGVHD after CBT were 11.6% and 18.0%. 24,25 In our study, cGVHD occurred in 5 of the 21 CBT patients (24%).…”

Section: Discussionmentioning

confidence: 46%

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2016

Exp Clin Transplant

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Objectives: We aimed to evaluate the safety of total body irradiation before bone marrow transplant. Materials and Methods: We analyzed 110 patients (65 male, 45 female) who underwent total body irradiation for hematopoietic stem cell transplant between May 1998 and March 2013. Median age at total body irradiation was 17 years (range, 1-62 y). Median observation time was 777 days (range, 31-5494 d). Initial diagnoses were acute lymphoblastic leukemia (24 patients), acute myeloid leukemia (26 patients), chronic myeloid leukemia (7 patients), myelodysplastic syndrome (8 patients), malignant lymphoma (13 patients), mucopolysaccharidosis (12 patients), neuroblastoma (10 patients), and other diseases (10 patients). The total fractionated dose used for total body irradiation was 12 Gy in 69 patients and 6.0-10.8 Gy in 29 patients. Single-dose total body irradiation was administered to 12 patients. Most patients (63 of 110) received chemotherapy consisting of cyclophosphamide alone. Results: Ocular complications were observed in 29.5% of the patients. Hypothyroidism, interstitial pneumonia, obliterative bronchiolitis, and veno-occlusive disease developed in 8.2%, 1.8%, 0.9%, and 2.7% of patients. Growth abnormality was observed in 10 (20%) of the 50 pediatric patients. The use of a lower dose (< 12 Gy vs 12 Gy) of fractionated total body irradiation did not decrease the incidence of adverse events; however, nonmyeloablative conditioning with low-dose singlefraction total body irradiation reduced the incidence of adverse events. Three patients who underwent total body irradiation as reirradiation therapy achieved long-term survival without adverse events. Conclusions: Fractionated total body irradiation given at a lower dose (<12 Gy vs 12 Gy) did not decrease the incidence of adverse events.

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Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics, predictive factors and impact on post‐transplant outcome

Cited by 15 publications

References 28 publications

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report

Clinical Utility of Quantitative PCR for Chimerism and Engraftment Monitoring after Allogeneic Stem Cell Transplantation for Hematologic Malignancies

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